New evidences on the altered gut microbiota in autism spectrum disorders

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Abstract

Background

Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology.

Results

Here, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure. A fraction of 90% of the autistic subjects were classified as severe ASDs. We found a significant increase in the Firmicutes/ Bacteroidetes ratio in autistic subjects due to a reduction of the Bacteroidetes relative abundance. At the genus level, we observed a decrease in the relative abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella in the ASD cohort, while Collinsella, Corynebacterium, Dorea, and Lactobacillus were significantly increased. Constipation has been then associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by high levels of bacterial taxa belonging to Escherichia/Shigella and Clostridium cluster XVIII. We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects, yet due to a larger dispersion of values, this difference was only partially significant.

Conclusions

The finding that, besides the bacterial gut microbiota, also the gut mycobiota contributes to the alteration of the intestinal microbial community structure in ASDs opens the possibility for new potential intervention strategies aimed at the relief of gastrointestinal symptoms in ASDs.

Electronic supplementary material

The online version of this article (doi:10.1186/s40168-017-0242-1) contains supplementary material, which is available to authorized users.

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Most cited references 38

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Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis.

Iliyan Iliev, Vincent Funari, Kent D. Taylor … (2012)

The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.

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Gastrointestinal flora and gastrointestinal status in children with autism -- comparisons to typical children and correlation with autism severity

James Adams, Leah Johansen, Linda D Powell … (2011)

Background Children with autism have often been reported to have gastrointestinal problems that are more frequent and more severe than in children from the general population. Methods Gastrointestinal flora and gastrointestinal status were assessed from stool samples of 58 children with Autism Spectrum Disorders (ASD) and 39 healthy typical children of similar ages. Stool testing included bacterial and yeast culture tests, lysozyme, lactoferrin, secretory IgA, elastase, digestion markers, short chain fatty acids (SCFA's), pH, and blood presence. Gastrointestinal symptoms were assessed with a modified six-item GI Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with the Autism Treatment Evaluation Checklist (ATEC). Results Gastrointestinal symptoms (assessed by the 6-GSI) were strongly correlated with the severity of autism (assessed by the ATEC), (r = 0.59, p < 0.001). Children with 6-GSI scores above 3 had much higher ATEC Total scores than those with 6-GSI-scores of 3 or lower (81.5 +/- 28 vs. 49.0 +/- 21, p = 0.00002). Children with autism had much lower levels of total short chain fatty acids (-27%, p = 0.00002), including lower levels of acetate, proprionate, and valerate; this difference was greater in the children with autism taking probiotics, but also significant in those not taking probiotics. Children with autism had lower levels of species of Bifidobacter (-43%, p = 0.002) and higher levels of species of Lactobacillus (+100%, p = 0.00002), but similar levels of other bacteria and yeast using standard culture growth-based techniques. Lysozyme was somewhat lower in children with autism (-27%, p = 0.04), possibly associated with probiotic usage. Other markers of digestive function were similar in both groups. Conclusions The strong correlation of gastrointestinal symptoms with autism severity indicates that children with more severe autism are likely to have more severe gastrointestinal symptoms and vice versa. It is possible that autism symptoms are exacerbated or even partially due to the underlying gastrointestinal problems. The low level of SCFA's was partly associated with increased probiotic use, and probably partly due to either lower production (less sacchrolytic fermentation by beneficial bacteria and/or lower intake of soluble fiber) and/or greater absorption into the body (due to longer transit time and/or increased gut permeability).

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Pyrosequencing study of fecal microflora of autistic and control children.

Sydney M. Finegold, Scot Dowd, Viktoria Gontcharova … (2010)

There is evidence of genetic predisposition to autism, but the percent of autistic subjects with this background is unknown. It is clear that other factors, such as environmental influences, may play a role in this disease. In the present study, we have examined the fecal microbial flora of 33 subjects with various severities of autism with gastrointestinal symptoms, 7 siblings not showing autistic symptoms (sibling controls) and eight non-sibling control subjects, using the bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP) procedure. The results provide us with information on the microflora of stools of young children and a compelling picture of unique fecal microflora of children with autism with gastrointestinal symptomatology. Differences based upon maximum observed and maximum predicted operational taxonomic units were statistically significant when comparing autistic and control subjects with p-values ranging from <0.001 to 0.009 using both parametric and non-parametric estimators. At the phylum level, Bacteroidetes and Firmicutes showed the most difference between groups of varying severities of autism. Bacteroidetes was found at high levels in the severely autistic group, while Firmicutes were more predominant in the control group. Smaller, but significant, differences also occurred in the Actinobacterium and Proteobacterium phyla. Desulfovibrio species and Bacteroides vulgatus are present in significantly higher numbers in stools of severely autistic children than in controls. If the unique microbial flora is found to be a causative or consequent factor in this type of autism, it may have implications with regard to a specific diagnostic test, its epidemiology, and for treatment and prevention. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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Author and article information

Contributors

Carlotta De Filippo: carlotta.defilippo@ibba.cnr.it

Journal

Journal ID (nlm-ta): Microbiome

Journal ID (iso-abbrev): Microbiome

Title: Microbiome

Publisher: BioMed Central (London )

ISSN (Electronic): 2049-2618

Publication date (Electronic): 22 February 2017

Publication date PMC-release: 22 February 2017

Publication date Collection: 2017

Volume: 5

Electronic Location Identifier: 24

Affiliations

[1 ]ISNI 0000 0004 1755 6224, GRID grid.424414.3, Computational Biology Research Unit, Research and Innovation Centre, , Fondazione Edmund Mach, ; Via E. Mach 1, 38010 San Michele all’ Adige, Italy

[2 ]ISNI 0000 0004 1937 0351, GRID grid.11696.39, Centre for Integrative Biology, , University of Trento, ; Via Sommarive 9, 38123 Trento, Italy

[3 ]ISNI 0000 0004 1757 2304, GRID grid.8404.8, Department of Biology, , University of Florence, ; Via Madonna del Piano 6, 50019 Sesto Fiorentino, Florence Italy

[4 ]ISNI 0000 0004 1759 0844, GRID grid.411477.0, Neonatal Intensive Care Unit, , Siena University Hospital AOUS, ; Viale Bracci 16, 53100 Siena, Italy

[5 ]ISNI 0000 0004 1759 0844, GRID grid.411477.0, Child Neuropsychiatry Unit, , Siena University Hospital AOUS, ; Viale Bracci 16, 53100 Siena, Italy

[6 ]Azienda Unità Sanitaria Locale Umbria 2, Via D. Bramante 37, 05100 Terni, Italy

[7 ]ISNI 0000 0004 1757 2304, GRID grid.8404.8, Department of Experimental and Clinical Biomedical Sciences, Gastroenterology Unit, , University of Florence, ; Viale Morgagni 40, 50139 Florence, Italy

[8 ]ISNI 0000 0001 1940 4177, GRID grid.5326.2, Institute of Agriculture Biology and Biotechnology, , National Research Council (CNR), ; Via Moruzzi 1, 56124 Pisa, Italy

Article

Publisher ID: 242

DOI: 10.1186/s40168-017-0242-1

PMC ID: 5320696

PubMed ID: 28222761

SO-VID: edd6c714-488c-4335-a9d6-086ae6601a6e

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 20 September 2016

Date accepted : 7 February 2017

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Keywords: autism spectrum disorders,gut microbiota,mycobiota,constipation,metataxonomy

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Keywords: autism spectrum disorders, gut microbiota, mycobiota, constipation, metataxonomy

New evidences on the altered gut microbiota in autism spectrum disorders

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Abstract

Background

Results

Conclusions

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Tick microbiome

Most cited references 38

Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis.

Gastrointestinal flora and gastrointestinal status in children with autism -- comparisons to typical children and correlation with autism severity

Pyrosequencing study of fecal microflora of autistic and control children.

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